Impact of Triple Combination CFTR Therapy on Sinus Disease.

Impact of Elexacaftor-tezacaftor-ivacaftor Triple Combination CFTR Therapy on Sinus Disease: Quantitative Sinus Computed Tomography, Patient Reported Outcomes and Cellular and Molecular Changes

The study's main goal is to observe how effective elexacaftor-tezacaftor-ivacaftor is for improving the symptoms and signs of CF-related sinus disease.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Elexacaftor-tezacaftor-ivacaftor exposure

Detailed Description

To determine if elexacfator-tezacaftor-ivacaftor improves the signs and symptoms of CF-related sinus disease, before and after initiation of triple combination therapy, each subject will undergo sinus CT scan and complete questionnaires related to signs and symptoms of sinus disease.

• Study Type: Observational
• Enrollment (Anticipated): 31

Contacts and Locations

• Study Contact: Name: Connor Balkissoon; Phone Number: 2768 877-225-5654; Email: balkissoonc@njhealth.org

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
      • Contact: Connor Balkissoon; Phone Number: 303-270-2768; Email: balkissoonc@njhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People with cystic fibrosis and chronic sinusitis.

Description

Inclusion Criteria:

1. Subjects from 18 to 89 years old.
2. Subjects with cystic fibrosis and comorbid chronic sinus disease (historic diagnosis based on physician assessment of signs and symptoms and medical record).
3. Subjects who clinically elect to initiate elexacaftor-tezacaftor-ivacaftor therapy and/or that are ineligible for CFTR modulator therapy based on their genotype, but have class I/II mutations based on sweat chloride > 90 mmol/L.

Exclusion Criteria:

1. Subjects under the age of 18 or over the age of 89.
2. Subjects who do not elect to initiate elexacaftor-tezacaftor-ivacaftor for clinical reasons.
3. Subjects who had sinus surgery within the last 6 months or will have sinus surgery during the study period.
4. Subjects who have had a recent pulmonary exacerbation or viral infection within two weeks of initial visit.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prescribed triple combination; A group of 60 people with CF who are clinically prescribed elexacaftor-tezacaftor-ivacaftor and have chronic sinusitis	Drug: Elexacaftor-tezacaftor-ivacaftor exposure; Once a clinical decision has been made to prescribed a patient triple combination therapy, people with CF are eligible to participate in this study.
Not eligible for modulators; A group of 10 patients with two class I/II mutations who are ineligible for elexacaftor-tezacaftor-ivacaftor based on their genotype and have chronic sinusitis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sinus CT opacification.	Calculated from an automated quantification of the size of sinuses.	Change in Sinus CT opacification between the initial and 6 month visits.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 22-item Sino-Nasal Outcome Test (SNOT-22) score.	Validated, disease-specific measure of sinus symptoms. Contains 22 questions that are all scored from 0 to 5, when summed a total score ranges form 0 to 110. Higher scores represent worse sinus symptoms.	Change in SNOT-22 score between the initial and 6 month visits.
Change in Questionnaire for Olfactory Disorders (QOD) score	Validated, disease-specific measure of olfaction, i.e. the ability to smell. Contains 19 questions that are scored form 0 to 3, when summed a total score can range form 0 to 57. Higher scores indicate greater impact on a subjects sense of smell.	Change in QOD score between the initial and 6 month visits.

Collaborators and Investigators

• Sponsor: Jennifer Taylor-Cousar
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jennifer TaylorCousar, M.D., National Jewish Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 5, 2019
• Primary Completion (ANTICIPATED): July 1, 2021
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: July 27, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (ACTUAL): August 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Sinusitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Nose Diseases; Pancreatic Diseases; Cystic Fibrosis; Paranasal Sinus Diseases; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor; Elexacaftor
• Other Study ID Numbers: HS-3236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes